RECRUITING

Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (SA-AKI)

Conditions

Acute Kidney Injury Due to Sepsis Sepsis acute kidney injury anti-inflammatory immunosuppression intensive care unit

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this Ph2b study is to characterize the dose-response relationship and to evaluate the safety and efficacy of three different single doses of TIN816 in hospitalized adult participants in an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI).

Official Title

A Multicenter, Randomized, Double-blind, Placebo-controlled, Four-arm, Parallel-group, Dose-finding Phase 2b Study to Investigate the Safety and Efficacy of TIN816 Via a Single Intravenous Infusion in the Treatment of Participants With Sepsis-associated Acute Kidney Injury (SA-AKI)

Quick Facts

Study Start:2024-01-18

Study Completion:2026-02-20

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05996835

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 85 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Signed informed consent must be obtained prior to participation in the study. 2. ≥ 18 to ≤ 85 years of age 3. Admitted to ICU or intermediate care unit/ high dependency care unit (HDU) 4. Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on: * Suspected or confirmed infection AND * Acute increase of SOFA score of 2 or more (excluding renal component). The baseline SOFA score should be assumed to be zero unless the participant is known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection 5. Diagnosis of AKI Stage 1 or greater per the following criterion at randomization: * For participants with hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI diagnosis should be used as the reference serum creatinine. * For participants presenting from community, the reference serum creatinine should be estimated using the following order of preference: 1. The most recent value within 3 months of the hospital admission. If not available: 2. The most recent value between 3 and 12 months prior to hospital admission. If not available: 3. At hospital admission 1. Not expected to survive for 24 hours 2. Not expected to survive for 30 days due to medical conditions other than SA-AKI 3. History of CKD with a documented estimated GFR \<45 mL/min prior to admission to hospital 4. eGFR \<45mL/min at admission without any other reference serum eGFR within last 12-months 5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization 6. Weight is less than 40 kg or more than 125 kg. 7. Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes (N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate orders are not an exclusion criterion unless associated with likely poor outcome in next 24 hours) 8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission 9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU 10. Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria 11. Presence of AKI, in the Investigator's opinion, as suggested by clinical manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission without a history of CKD, for a period longer than 24 hours prior to study drug administration 12. Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization 13. AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides, etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal artery stenosis), urinary obstruction 14. Documented (biopsy proven) or suspected history of acute or sub-acute kidney diseases such as rapidly progressive glomerular nephritis (RPGN) and acute interstitial nephritis (AIN) 15. Patients who are post-nephrectomy 16. Patients with permanent incapacitation 17. Patients who are thrombocytopenic at screening (platelet count \<50,000 per microliter) who have active/uncontrolled bleeding or who present current or past conditions indicating high risk for bleeding in the opinion of the investigator (e.g. coagulopathies, previous history of major non-traumatic bleeding etc.) 18. Immunosuppressed patients * History of immunodeficiency diseases * Receiving immunosuppressant treatment or on chronic high doses (high-dose therapy exceeding 2 weeks of treatment) of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with corticosteroids (as per the Surviving Sepsis Guidelines) can be included. See Appendix Section 10.6 Immunosuppresant drugs, (Table 10 5 Immunosuppressant drug exclusions) 19. Patients with known or presumed latent or active TB based on clinical history or imaging e.g. patients on TB preventive therapy or close/household contacts of pulmonary TB patients 20. Known active hepatitis B or C infection, or positive Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) serology or patients with advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C) 21. Acute pancreatitis with no established source of infection 22. Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable) 23. Burns requiring ICU treatment 24. Sepsis attributed to confirmed COVID-19 25. Use of other investigational drugs within 5 half-lives of enrollment, within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations 26. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes 27. Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement 28. Women with a positive pregnancy test, pregnancy or breast feeding 29. Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.	Pregnancy or breastfeeding Severe psychiatric disorders Active substance abuse Unstable medical conditions Inability to comply with study requirements

Inclusion Criteria

Exclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. ≥ 18 to ≤ 85 years of age
3. Admitted to ICU or intermediate care unit/ high dependency care unit (HDU)
4. Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on:
* Suspected or confirmed infection AND
* Acute increase of SOFA score of 2 or more (excluding renal component). The baseline SOFA score should be assumed to be zero unless the participant is known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection
5. Diagnosis of AKI Stage 1 or greater per the following criterion at randomization:
* For participants with hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI diagnosis should be used as the reference serum creatinine.
* For participants presenting from community, the reference serum creatinine should be estimated using the following order of preference:
1. The most recent value within 3 months of the hospital admission. If not available:
2. The most recent value between 3 and 12 months prior to hospital admission. If not available:
3. At hospital admission
1. Not expected to survive for 24 hours
2. Not expected to survive for 30 days due to medical conditions other than SA-AKI
3. History of CKD with a documented estimated GFR \<45 mL/min prior to admission to hospital
4. eGFR \<45mL/min at admission without any other reference serum eGFR within last 12-months
5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization
6. Weight is less than 40 kg or more than 125 kg.
7. Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes (N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate orders are not an exclusion criterion unless associated with likely poor outcome in next 24 hours)
8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission
9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU
10. Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria
11. Presence of AKI, in the Investigator's opinion, as suggested by clinical manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission without a history of CKD, for a period longer than 24 hours prior to study drug administration
12. Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization
13. AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides, etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal artery stenosis), urinary obstruction
14. Documented (biopsy proven) or suspected history of acute or sub-acute kidney diseases such as rapidly progressive glomerular nephritis (RPGN) and acute interstitial nephritis (AIN)
15. Patients who are post-nephrectomy
16. Patients with permanent incapacitation
17. Patients who are thrombocytopenic at screening (platelet count \<50,000 per microliter) who have active/uncontrolled bleeding or who present current or past conditions indicating high risk for bleeding in the opinion of the investigator (e.g. coagulopathies, previous history of major non-traumatic bleeding etc.)
18. Immunosuppressed patients
* History of immunodeficiency diseases
* Receiving immunosuppressant treatment or on chronic high doses (high-dose therapy exceeding 2 weeks of treatment) of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with corticosteroids (as per the Surviving Sepsis Guidelines) can be included. See Appendix Section 10.6 Immunosuppresant drugs, (Table 10 5 Immunosuppressant drug exclusions)
19. Patients with known or presumed latent or active TB based on clinical history or imaging e.g. patients on TB preventive therapy or close/household contacts of pulmonary TB patients
20. Known active hepatitis B or C infection, or positive Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) serology or patients with advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C)
21. Acute pancreatitis with no established source of infection
22. Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable)
23. Burns requiring ICU treatment
24. Sepsis attributed to confirmed COVID-19
25. Use of other investigational drugs within 5 half-lives of enrollment, within 30 days (e.g., small molecules) or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations
26. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes
27. Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement
28. Women with a positive pregnancy test, pregnancy or breast feeding
29. Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.

Pregnancy or breastfeeding
Severe psychiatric disorders
Active substance abuse
Unstable medical conditions
Inability to comply with study requirements

Contacts and Locations

Study Contact

Novartis Pharmaceuticals

CONTACT

1-888-669-6682

novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

Principal Investigator

Novartis Pharmaceuticals

STUDY_DIRECTOR

Novartis Pharmaceuticals

Study Locations (Sites)

UC San Francisco Medical Center

San Francisco, California, 94143-0116

United States

Northwestern Memorial Hospital Pulmonary and Critical Care

Evanston, Illinois, 60611

United States

Univ Of Iowa Hospitals And Clinics

Iowa City, Iowa, 52242

United States

Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805

United States

Baystate Medical Center

Springfield, Massachusetts, 01199

United States

Henry Ford Hospital

Detroit, Michigan, 48202 2689

United States

Mayo Clinic Rochester Main Centre

Rochester, Minnesota, 55905

United States

Montefiore Medical Center

Bronx, New York, 10461

United States

Montefiore Medical Center Montefiore Medical Center

Bronx, New York, 10467

United States

Wake Forest Univ School of Medicine U Health Sciences

Winston-Salem, North Carolina, 27157-1071

United States

Ohio State University Medical Center

Columbus, Ohio, 43210

United States

Good Samaritan Hospital

Corvallis, Oregon, 97330

United States

Temple University Temple University

Philadelphia, Pennsylvania, 19140

United States

Baylor Scott and White Research

Dallas, Texas, 75246

United States

Utah Intermountain Medical Center

Murray, Utah, 84107

United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

Novartis Pharmaceuticals, STUDY_DIRECTOR, Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-01-18

Study Completion Date2026-02-20

Study Record Updates

Study Start Date2024-01-18

Study Completion Date2026-02-20

Terms related to this study

Keywords Provided by Researchers

Sepsis
acute kidney injury
anti-inflammatory
immunosuppression
intensive care unit

Additional Relevant MeSH Terms

Acute Kidney Injury Due to Sepsis